Incidental Mutation 'IGL00795:Tbcd'

• ID: 14389
• Institutional Source: Australian Phenomics Network
• Gene Symbol: Tbcd
• Ensembl Gene: ENSMUSG00000039230
• Gene Name: tubulin-specific chaperone d
• Synonyms: 2310057L06Rik, A030005L14Rik
• Essential gene?: Probably essential (E-score: 0.957)
• Stock #: IGL00795
• Chromosome: 11
• Chromosomal Location: 121342817-121507996 bp(+) (GRCm39)
• Type of Mutation: missense
• DNA Base Change (assembly): T to G at 121507758 bp (GRCm39)
• Zygosity: Heterozygous
• Amino Acid Change: Isoleucine to Serine at position 1193 (I1193S)
• Ref Sequence: ENSEMBL: ENSMUSP00000099302
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000067399] [ENSMUST00000103013]
• AlphaFold: Q8BYA0
• Predicted Effect: probably benign; Transcript: ENSMUST00000067399
• SMART Domains: Protein: ENSMUSP00000068590; Gene: ENSMUSG00000046605

Domain	Start	End	E-Value	Type
Pfam:Glyco_tranf_2_3	14	245	1.4e-10	PFAM
Pfam:Glycos_transf_2	17	189	1.2e-23	PFAM
Pfam:Glyco_tranf_2_2	17	248	2.1e-8	PFAM

• Predicted Effect: probably benign; Transcript: ENSMUST00000103013; AA Change: I1193S; PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
• SMART Domains: Protein: ENSMUSP00000099302; Gene: ENSMUSG00000039230; AA Change: I1193S

Domain	Start	End	E-Value	Type
low complexity region	6	20	N/A	INTRINSIC
low complexity region	45	62	N/A	INTRINSIC
SCOP:d1b3ua_	357	742	4e-20	SMART
Pfam:TFCD_C	900	1090	1.4e-74	PFAM
low complexity region	1113	1120	N/A	INTRINSIC

• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000139414
• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000151666
• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000155666
• MGI Phenotype: FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]
• Allele List at MGI:

  All alleles(23) : Gene trapped(23)

• Posted On: 2012-12-06
• Science Writer: Anne Murray

Protein Function and Prediction

Tbcd encodes tubulin folding cofactor D (TBCD), a member of the tubulin synthesis complex (1). TBCD modulates microtubule dynamics by sequestering β-tubulin from GTP-bound αβ-heterodimers (2). Fanarraga et al. determined that TBCD has a role in centriologenesis, spindle organization, and cell abcission (1). TBCD depletion results in mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis (1). Human TBCD is proposed to recruite cytosolic centrosomal proteins (e.g., pericentrin or γ-tubulin) to the mitotic spindle (3). Mutations in TBCD have been linked to chromosome number aberrations, G1/S blockage, spindle pole body separation, and abnormal cytokinesis in yeast, Arabidopsis, and Caenorhabditis elegans (4-10). TBCD is ubiquitously expressed in human tissues tested (i.e., brain, spinal cord, liver, pancreas, kidney, spleen, heart, lung, skeletal muscle, testis, ovary, fetal brain, and fetal liver) by RT-PCR followed by ELISA (11). The TBCD protein is localized throughout the cell (2). Further studies determined that TBCD is concentrated at the centrosome and midbody (1). Furthermore, TBCD localization is cell-cycle-specific with localization on the daughter centriole at G1 and on procentrioles by S; TBCD disappears from older centrioles at telophase as the protein is recruited to the midbody (1). At the onset of the centrosome duplication cycle, TBCD is recruited to the centriole replication site (1). During cytokinesis TBCD is localized at Fleming bodies at the midbody (1).

References

  1. Fanarraga, M. L., Bellido, J., Jaen, C., Villegas, J. C., and Zabala, J. C. (2010) TBCD Links Centriologenesis, Spindle Microtubule Dynamics, and Midbody Abscission in Human Cells. PLoS One. 5, e8846.

  2. Martin, L., Fanarraga, M. L., Aloria, K., and Zabala, J. C. (2000) Tubulin Folding Cofactor D is a Microtubule Destabilizing Protein. FEBS Lett. 470, 93-95.

  3. Cunningham, L. A., and Kahn, R. A. (2008) Cofactor D Functions as a Centrosomal Protein and is Required for the Recruitment of the Gamma-Tubulin Ring Complex at Centrosomes and Organization of the Mitotic Spindle. J Biol Chem. 283, 7155-7165.

  4. Hirata, D., Masuda, H., Eddison, M., and Toda, T. (1998) Essential Role of Tubulin-Folding Cofactor D in Microtubule Assembly and its Association with Microtubules in Fission Yeast. EMBO J. 17, 658-666.

  5. Hoyt, M. A., Stearns, T., and Botstein, D. (1990) Chromosome Instability Mutants of Saccharomyces Cerevisiae that are Defective in Microtubule-Mediated Processes. Mol Cell Biol. 10, 223-234.

  6. Sonnichsen, B., Koski, L. B., Walsh, A., Marschall, P., Neumann, B., Brehm, M., Alleaume, A. M., Artelt, J., Bettencourt, P., Cassin, E., Hewitson, M., Holz, C., Khan, M., Lazik, S., Martin, C., Nitzsche, B., Ruer, M., Stamford, J., Winzi, M., Heinkel, R., Roder, M., Finell, J., Hantsch, H., Jones, S. J., Jones, M., Piano, F., Gunsalus, K. C., Oegema, K., Gonczy, P., Coulson, A., Hyman, A. A., and Echeverri, C. J. (2005) Full-Genome RNAi Profiling of Early Embryogenesis in Caenorhabditis Elegans. Nature. 434, 462-469.

  7. Fedyanina, O. S., Book, A. J., and Grishchuk, E. L. (2009) Tubulin Heterodimers Remain Functional for One Cell Cycle After the Inactivation of Tubulin-Folding Cofactor D in Fission Yeast Cells. Yeast. 26, 235-247.

  8. Fedyanina, O. S., Mardanov, P. V., Tokareva, E. M., McIntosh, J. R., and Grishchuk, E. L. (2006) Chromosome Segregation in Fission Yeast with Mutations in the Tubulin Folding Cofactor D. Curr Genet. 50, 281-294.

  9. Steinborn, K., Maulbetsch, C., Priester, B., Trautmann, S., Pacher, T., Geiges, B., Kuttner, F., Lepiniec, L., Stierhof, Y. D., Schwarz, H., Jurgens, G., and Mayer, U. (2002) The Arabidopsis PILZ Group Genes Encode Tubulin-Folding Cofactor Orthologs Required for Cell Division but Not Cell Growth. Genes Dev. 16, 959-971.

  10. Srayko, M., Kaya, A., Stamford, J., and Hyman, A. A. (2005) Identification and Characterization of Factors Required for Microtubule Growth and Nucleation in the Early C. Elegans Embryo. Dev Cell. 9, 223-236.

  11. Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. (1999) Prediction of the Coding Sequences of Unidentified Human Genes. XIII. the Complete Sequences of 100 New cDNA Clones from Brain which Code for Large Proteins in Vitro. DNA Res. 6, 63-70.